A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS
A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS
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HPLC-MS/MS法比较5-羟基-4-甲氧基斑素-6-酮及其代谢物在正常大鼠和右旋糖酐硫酸钠诱导结肠炎大鼠体内的药代动力学和组织分布
DOI：
10.1111/jphp.13285
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发表时间：
2020-05-03
影响因子：
3.3
通讯作者：
Zhu, Chenchen
中科院分区：
文献类型：
--
作者：
Liu, Fangle;Zhang, Qiuyu;Zhu, Chenchen
目的研究口服5-羟基-4-甲氧基角黄素-6-酮（5-hydroxy-4-methoxycanthin-6-one，PQ-A）后在体内的存在形式，以及结肠炎对其药代动力学和组织分布的影响。在从口服给予PQ-A的正常和葡聚糖硫酸钠（DSS）诱导的结肠炎大鼠获得的生物样品中。结果表明，PQ-A在生理和病理状态下均以原型存在，PQ-B在体内的分布与PQ-A的原型存在密切相关。PQ-A在结肠炎大鼠体内的暴露量和消除时间均明显高于正常大鼠。提示肠炎对治疗结肠炎药物的药代动力学有影响。组织分布研究表明，PQ-A主要在肠道内蓄积。结论本实验结果有助于进一步阐明PQ-A在不同病理状态下的ADME过程，为临床应用类似药物提供参考。
Objectives This study aimed to investigate the existing form of 5-hydroxy-4-methoxycanthin-6-one (PQ-A) in vivo after oral administration and the effects on its pharmacokinetics and tissue distribution by colitis.Methods A rapid HPLC-MS/MS method was established to simultaneously determine PQ-A and its main metabolite, 1-methoxicabony-beta-carboline (PQ-B), in biological samples acquired from normal and dextran sodium sulfate (DSS)-induced colitic rats administered orally with PQ-A. Then, the pharmacokinetics of both PQ-A and PQ-B, and tissue distribution of PQ-A in the above two states were analysed.Key findings The pharmacokinetic results showed that the prototype of PQ-A was the main existing form in both physiological and pathological conditions. And significant difference between the above two status in pharmacokinetics of PQ-A was observed, such as higher exposure and longer elimination in colitis than that in normal rats. It suggested that the pharmacokinetics of medications for colitis was affected by enteritis. The tissue distribution studies displayed that PQ-A mainly accumulated in intestinal tract. Especially, the distribution of PQ-A in intestinal tract was increased obviously in colitic rats.Conclusions These results contributed to further illuminate the ADME process of PQ-A in different status and were prospected to be the reference to the clinical application of similar medicines in pathological states.